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MetaCyc Pathway: superpathway of N-acetylneuraminate degradation
Inferred from experiment

Pathway diagram: superpathway of N-acetylneuraminate degradation

Note: a dashed line (without arrowheads) between two compound names is meant to imply that the two names are just different instantiations of the same compound -- i.e. one may be a specific name and the other a general name, or they may both represent the same compound in different stages of a polymerization-type pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: N-acetylneuraminate catabolism, sialic acid degradation

Superclasses: Degradation/Utilization/AssimilationCarboxylates Degradation

Some taxa known to possess this pathway include : Abiotrophia defectiva, Clostridium perfringens, Clostridium perfringens 13, Clostridium perfringens A99Inferred from experiment [Kruger01], Escherichia coli K-12 substr. MG1655, Streptococcus anginosus, Streptococcus constellatus, Streptococcus gordonii, Streptococcus intermedius, Streptococcus mitis, Streptococcus oralis, Streptococcus sanguinis

Expected Taxonomic Range: Bacteria

Several viridans streptococci, such as Streptococcus oralis, are able to enter the bloodstream through dental caries and cause several serious infections, including endocarditis, brain abscesses and, in immunocompromised patients, septicaemia [Straus77, Ochiai99, Byers99].

The exact mechanisms by which these organisms proliferate in vivo are unknown. One of the potential sources of fermentable carbohydrate are host-derived sialic acids such as N-acetylneuraminate, which is present in serum, and can be liberated from glycoproteins and other sialoglyoconjugates via the action of sialidases [Beighton90, Byers00].

Several species of the viridans streptococci, including Abiotrophia defectiva, Streptococcus anginosus, Streptococcus constellatus, Streptococcus gordonii, Streptococcus intermedius, Streptococcus mitis, Streptococcus oralis and Streptococcus sanguinis are able to utilize N-acetylneuraminate as a sole carbon source, independently of sialidase production [Byers96]. The major end products of N-acetylneuraminate metabolism in these organisms are formate, acetate and ethanol.

A transport system for N-acetylneuraminate was characterized in Streptococcus oralis [Byers99]. This system followed typical Michaelis-Menten kinetics, with a Km of 21.0 μM and a Vmax of 2.65 nmoles/min/mg of dry cell mass.

The pathway for the degradation of N-acetylneuraminate has been studied in viridans streptococci, and its first part is essentially identical to the pathway found in Escherichia coli K-12 (see superpathway of N-acetylglucosamine, N-acetylmannosamine and N-acetylneuraminate degradation). The first step of the pathway consists of splitting of N-acetylneuraminate into N-acetyl-β-D-mannosamine and pyruvate, catalyzed by the enzyme N-acetylneuraminate lyase. N-acetyl-β-D-mannosamine is then phosphorylated to N-acetyl-D-mannosamine 6-phosphate. Next the acetyl group is removed (by N-acetylglucosamine-6-phosphate deacetylase), followed by removal of the ammoium group (by glucosamine-6-phosphate deaminase), resulting in formation of β-D-fructofuranose 6-phosphate, which enters glycolysis for substrate level phosphorylation.

In oral streptococci the end product of glycolysis, pyruvate, can be fermented into either (S)-lactate or to formate, acetate and ethanol. When grown on N-acetylneuraminate no lactate is produced, and only the later three products are observed [Byers96].

Subpathways: glycolysis II (from fructose 6-phosphate), N-acetylglucosamine degradation I, N-acetylneuraminate and N-acetylmannosamine degradation I, pyruvate fermentation to ethanol I, pyruvate fermentation to acetate IV, acetate formation from acetyl-CoA I

Created 08-Mar-2001 by Pellegrini-Toole A, Marine Biological Laboratory
Revised 22-Mar-2007 by Caspi R, SRI International


Angata02: Angata T, Varki A (2002). "Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective." Chem Rev 102(2);439-69. PMID: 11841250

Beighton90: Beighton D, Whiley RA (1990). "Sialidase activity of the "Streptococcus milleri group" and other viridans group streptococci." J Clin Microbiol 28(6);1431-3. PMID: 2199505

Byers00: Byers HL, Tarelli E, Homer KA, Beighton D (2000). "Isolation and characterisation of sialidase from a strain of Streptococcus oralis." J Med Microbiol 49(3);235-44. PMID: 10707943

Byers96: Byers HL, Homer KA, Beighton D (1996). "Utilization of sialic acid by viridans streptococci." J Dent Res 1996;75(8);1564-71. PMID: 8906124

Byers99: Byers HL, Homer KA, Tarelli E, Beighton D (1999). "N-acetylneuraminic acid transport by Streptococcus oralis strain AR3." J Med Microbiol 48(4);375-81. PMID: 10509480

Cox02: Cox AD, Hood DW, Martin A, Makepeace KM, Deadman ME, Li J, Brisson JR, Moxon ER, Richards JC (2002). "Identification and structural characterization of a sialylated lacto-N-neotetraose structure in the lipopolysaccharide of Haemophilus influenzae." Eur J Biochem 269(16);4009-19. PMID: 12180977

Hood99: Hood DW, Makepeace K, Deadman ME, Rest RF, Thibault P, Martin A, Richards JC, Moxon ER (1999). "Sialic acid in the lipopolysaccharide of Haemophilus influenzae: strain distribution, influence on serum resistance and structural characterization." Mol Microbiol 33(4);679-92. PMID: 10447878

Kruger01: Kruger D, Schauer R, Traving C (2001). "Characterization and mutagenesis of the recombinant N-acetylneuraminate lyase from Clostridium perfringens: insights into the reaction mechanism." Eur J Biochem 268(13);3831-9. PMID: 11432751

Ochiai99: Ochiai K, Kikuchi K, Fukushima K, Kurita-Ochiai T (1999). "Co-aggregation as a virulent factor of Streptococcus sanguis isolated from infective endocarditis." J Oral Sci 41(3);117-22. PMID: 10692836

Severi05: Severi E, Randle G, Kivlin P, Whitfield K, Young R, Moxon R, Kelly D, Hood D, Thomas GH (2005). "Sialic acid transport in Haemophilus influenzae is essential for lipopolysaccharide sialylation and serum resistance and is dependent on a novel tripartite ATP-independent periplasmic transporter." Mol Microbiol 58(4);1173-85. PMID: 16262798

Severi08: Severi E, Muller A, Potts JR, Leech A, Williamson D, Wilson KS, Thomas GH (2008). "Sialic acid mutarotation is catalysed by the Escherichia coli beta -propeller protein YJHT." J Biol Chem 283(8):4841-9. PMID: 18063573

Straus77: Straus DC, Mattingly SJ, Milligan TW (1977). "Production of extracellular material by streptococci associated with subacute bacterial endocarditis." Infect Immun 17(1);148-56. PMID: 885611

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Abbe83: Abbe K, Takahashi S, Yamada T (1983). "Purification and properties of pyruvate kinase from Streptococcus sanguis and activator specificity of pyruvate kinase from oral streptococci." Infect Immun 39(3);1007-14. PMID: 6840832

Acebron09: Acebron SP, Martin I, del Castillo U, Moro F, Muga A (2009). "DnaK-mediated association of ClpB to protein aggregates. A bichaperone network at the aggregate surface." FEBS Lett 583(18);2991-6. PMID: 19698713

Aceti88: Aceti DJ, Ferry JG (1988). "Purification and characterization of acetate kinase from acetate-grown Methanosarcina thermophila. Evidence for regulation of synthesis." J Biol Chem 1988;263(30);15444-8. PMID: 2844814

Aguilera09: Aguilera L, Gimenez R, Badia J, Aguilar J, Baldoma L (2009). "NAD+-dependent post-translational modification of Escherichia coli glyceraldehyde-3-phosphate dehydrogenase." Int Microbiol 12(3);187-92. PMID: 19784925

Aisaka91: Aisaka K, Igarashi A, Yamaguchi K, Uwajima T (1991). "Purification, crystallization and characterization of N-acetylneuraminate lyase from Escherichia coli." Biochem J 1991;276 ( Pt 2);541-6. PMID: 1646603

AitBara10: Ait-Bara S, Carpousis AJ (2010). "Characterization of the RNA degradosome of Pseudoalteromonas haloplanktis: conservation of the RNase E-RhlB interaction in the gammaproteobacteria." J Bacteriol 192(20);5413-23. PMID: 20729366

Al04: Al Zaid Siddiquee K, Arauzo-Bravo MJ, Shimizu K (2004). "Metabolic flux analysis of pykF gene knockout Escherichia coli based on 13C-labeling experiments together with measurements of enzyme activities and intracellular metabolite concentrations." Appl Microbiol Biotechnol 63(4);407-17. PMID: 12802531

Alakent11: Alakent B, Baskan S, Doruker P (2011). "Effect of ligand binding on the intraminimum dynamics of proteins." J Comput Chem 32(3);483-96. PMID: 20730777

Albery76: Albery WJ, Knowles JR (1976). "Free-energy profile of the reaction catalyzed by triosephosphate isomerase." Biochemistry 15(25);5627-31. PMID: 999838

Albin84: Albin R, Silverman PM (1984). "Physical and genetic structure of the glpK-cpxA interval of the Escherichia coli K-12 chromosome." Mol Gen Genet 197(2);261-71. PMID: 6097795

Alefounder89: Alefounder PR, Perham RN (1989). "Identification, molecular cloning and sequence analysis of a gene cluster encoding the class II fructose 1,6-bisphosphate aldolase, 3-phosphoglycerate kinase and a putative second glyceraldehyde 3-phosphate dehydrogenase of Escherichia coli." Mol Microbiol 3(6);723-32. PMID: 2546007

Alefounder89a: Alefounder PR, Baldwin SA, Perham RN, Short NJ (1989). "Cloning, sequence analysis and over-expression of the gene for the class II fructose 1,6-bisphosphate aldolase of Escherichia coli." Biochem J 1989;257(2);529-34. PMID: 2649077

AlmagroMoreno09: Almagro-Moreno S, Boyd EF (2009). "Insights into the evolution of sialic acid catabolism among bacteria." BMC Evol Biol 9;118. PMID: 19470179

Altamirano87: Altamirano MM, Mulliert G, Calcagno M (1987). "Sulfhydryl groups of glucosamine-6-phosphate isomerase deaminase from Escherichia coli." Arch Biochem Biophys 1987;258(1);95-100. PMID: 2821923

Altamirano90: Altamirano MM, Calcagno M (1990). "Zinc binding and its trapping by allosteric transition in glucosamine-6-phosphate deaminase from Escherichia coli." Biochim Biophys Acta 1038(3);291-4. PMID: 2111170

Altamirano92: Altamirano MM, Plumbridge JA, Calcagno ML (1992). "Identification of two cysteine residues forming a pair of vicinal thiols in glucosamine-6-phosphate deaminase from Escherichia coli and a study of their functional role by site-directed mutagenesis." Biochemistry 31(4);1153-8. PMID: 1734962

Altamirano93: Altamirano MM, Plumbridge JA, Barba HA, Calcagno ML (1993). "Glucosamine-6-phosphate deaminase from Escherichia coli has a trimer of dimers structure with three intersubunit disulphides." Biochem J 295 ( Pt 3);645-8. PMID: 8240271

Altamirano94: Altamirano MM, Hernandez-Arana A, Tello-Solis S, Calcagno ML (1994). "Spectrochemical evidence for the presence of a tyrosine residue in the allosteric site of glucosamine-6-phosphate deaminase from Escherichia coli." Eur J Biochem 1994;220(2);409-13. PMID: 8125098

Altamirano95: Altamirano MM, Plumbridge JA, Horjales E, Calcagno ML (1995). "Asymmetric allosteric activation of Escherichia coli glucosamine-6-phosphate deaminase produced by replacements of Tyr 121." Biochemistry 34(18);6074-82. PMID: 7742311

Aluri15: Aluri S, Rex K, Varshney U (2015). "Simultaneous presence of fhs and purT genes is disadvantageous for the fitness of Escherichia coli growth." FEMS Microbiol Lett 362(14). PMID: 26100103

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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